Among patients with newly diagnosed acute myeloid leukemia (AML), venetoclax plus low-dose cytarabine (LDAC) appears to yield improved outcomes compared with LDAC alone, according to research published in Blood.

Elderly patients with AML are frequently ineligible for intensive chemotherapy because of comorbidities, which limits the treatment options available to this patient population. Given that for patients with AML the median age at diagnosis is more than 68 years, novel therapies are needed.

Venetoclax, a selective and potent inhibitor of BCL2, which is linked with chemotherapy resistance in AML, has shown promising efficacy in phase 2 trials when combined with LDAC, which alone yields low response rates. For this randomized phase 3 trial, researchers evaluated the safety and efficacy of venetoclax with LDAC compared with placebo with LDAC in patients with previously untreated AML aged at least 75 years or those with comorbidities precluding intensive chemotherapy.

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The trial enrolled 211, of whom 210 received treatment; 143 were randomly assigned to receive venetoclax plus LDAC vs 68 who received placebo plus LDAC. In the venetoclax vs the placebo group, the median age was 76 in both, 55% vs 57%, respectively, were male, 59% vs 66% had de novo AML, and 64% vs 67% had favorable or intermediate cytogenetic risk scores.

The median follow-up for the preplanned primary analysis was 12 months in both groups. At analysis, 40% of patients assigned to the venetoclax arm vs 31% of those assigned to placebo were alive. The median overall survival (OS) with venetoclax was 7.2 months vs 4.1 months with placebo (P =.11).

On multivariate analysis, however, the hazard ratio for OS with venetoclax vs placebo was 0.67 (P =.03). More patients in the venetoclax arm (27%) had a complete response compared with those who received placebo (7%; P <.001). Median event-free survival was also improved with venetoclax (4.7 months vs 2 months with placebo; P =.002).

The most common grade 3 or worse hematologic adverse events (AEs) were neutropenia (46% with venetoclax vs 16% with placebo), thrombocytopenia (45% vs 37%, respectively), and febrile neutropenia (32% vs 29%). Other common AEs included nausea (42% with venetoclax vs 31% with placebo), hypokalemia (28% vs 22%, respectively), and diarrhea (28% vs 16%).

Thirty-three patients receiving venetoclax and 14 receiving placebo had an AE leading to death.

“In summary, the combination of venetoclax plus LDAC demonstrated a well-tolerated and manageable safety profile, together with clinically meaningful benefits in OS, rates of remission, [event-free survival], transfusion requirements, and patient-reported outcomes, compared with LDAC alone, in previously untreated patients with AML who were ineligible for intensive chemotherapy,” the authors wrote.


Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood. 2020;135(24):2137-45. doi: 10.1182/blood.2020004856